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VET - Pharm > Lec5 > Flashcards

Lec5 Flashcards

1
Q

Withdrawal Time

A

the period of time after drug administration during which the animal cannot be sent to market for slaughter as food and the eggs or milk must be discarded

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2
Q

Half Life

A

the time required for the amount of drug in the body to be reduced by 50% (usually expressed in hours and abbreviated T 1/2)

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3
Q

Steady State

A

the point at which drug accumulation and elimination are balanced

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4
Q

Pharmacokinetics

A

the study of the physiologic movement of drugs throughout the body; also includes the movement of substances across cell membranes.

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5
Q

The four steps in pharmacokinetics are:

A

Absorption

Distribution

Biotransformation

Excretion

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6
Q

Drug-blood/plasma levels are dependent upon

A

The rate at which the drug is absorbed into the blood stream.

The amount of drug that is absorbed into the blood stream.

The distribution of the drug throughout the body.

The biotransformation of the drug.

The rate and route of drug excretion.

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7
Q

Four basic mechanisms of drug movement across cell membranes include:

A

Passive Diffusion

Facilitated Diffusion

Active Transport

Pinocytosis/Phagocytosis

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8
Q

Passive Diffusion

A

movement of drug molecules from an area of high concentration to an area of low concentration

does not require or expend energy

drug molecules exchange at an even rate so there are equal numbers of molecules both inside and outside the cell

in theory, drug molecules move throughout the body until equilibrium is attained among all body compartments

requires the drug to dissolve in the cell membrane and pass through the cell membrane made primarily of phospholipid with small pores

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9
Q

Lipophilic (+some details of these drugs)

A

dissolves in fat or oil medium

Lipophilic drugs dissolve more readily into the phospholipid cell membranes such as the intestinal mucosa

Lipophilic drugs are well absorbed from the gut by passive diffusion

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10
Q

Hydrophilic (+some details of these drugs)

A

dissolves in water/aqueous medium

Do not pass through lipid rich membranes as easily

Are more readily absorbed in fluid surrounding cells and must diffuse through fluid to reach capillaries

Drugs given IM are ideally hydrophilic for better absorption

IM drugs may be formulated to be lipophilic in form for slower absorption

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11
Q

Ionization (how does this influence drugs/uptake)

A

also affects movement of drugs across cell membranes

Ionized drugs have either a positive or negative charge

Tend to be hydrophilic in form

Non-ionized drugs have no charge and are neutral

Tend to be lipophilic in form

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12
Q

What characteristics of water affinity and ionization lend to effective diffusion?

A

drug molecules that move most effectively across cell membranes are lipophilic/non-ionized

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13
Q

Facilitated Diffusion

A

like passive diffusion but utilizes a special carrier molecule

Carrier molecule helps drugs across the cell membrane

No energy is needed

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14
Q

Active Transport

A

specialized carrier molecules in cell membranes move the drug across the membrane

requires energy

can move against a concentration from areas of lower concentration to higher concentration

allows drugs to accumulate in high concentration within a cell or body compartment

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15
Q

Phagocytosis

A

cell eating that is helpful with large molecules such as proteins that cannot pass through intact membranes

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16
Q

Pinocytosis

A

cell drinking of liquid particles

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17
Q

Absorption

A

the passage of the drug from its site of administration into the bloodstream.

before drugs can reach the site of action, the membranes of the absorptive surfaces must be crossed

drugs that are directly administered into the blood supply do not have an absorptive phase because the drug is placed directly into the plasma compartment!

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18
Q

Bioavailability

A

the degree or percentage of a drug administered that actually enters the systemic circulation

reflects the route of administration and number of barriers the drug must cross and/or delays encountered in reaching therapeutic blood levels (IV>IM>SQ>PO)

drugs that have no barriers (would be considered 100% bioavailable (bioavailability number of 1)

drugs given IV or IA are 100% bioavailable

some drugs are designed to have poor or no bioavailability (topicals, local analgesics, oral dewormers)

the lower the bioavailability, the less drug in the circulation and tissues

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19
Q

factors that affects bioavailability include:

A

blood supply to the area

surface area of absorption

dosage form of the drug

mechanism of drug absorption

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20
Q

Drug factors that affect absorption are:

A

Drug Chemistry (lipophilic vs. hydrophilic)

Drug Size (smaller molecules pass easier)

Ionization of the drug (non-ionized pass phospholipid membranes, ionized diffuse through tissue fluid)

Acid-Base Characteristics (pH of the drug)

Ion Trapping

Drug Form

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21
Q

In an Acid Environment, an Acidic Drug is Predominately (ionization and water affinity)

A

Non-Ionized (Not Charged) and therefore Lipophilic

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22
Q

An Acid Drug in an Alkaline Environment is Predominately (ionization and water affinity)

A

Ionized and Hydrophilic

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23
Q

In an Alkaline environment, an Alkaline drug is (ionization and water affinity)

A

Non-ionized (Not Charged) and therefore Lipophilic

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24
Q

Alkaline Drugs in an Acid Environment are (ionization and water affinity)

A

Ionized (Charged) and therefore Hydrophilic

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25
Q

How does pH (drug/environment) affect ionization

A

The pH of a drug in the pH of an environment affects the ionization of that drug

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26
Q

Ion Trapping

A

drugs can pass from one compartment to another when the pH changes

When a drug changes compartments, it may become ionized and trapped in its new environment, so that it can be absorbed into the bloodstream

Ion trapping is especially important in drug excretion, since alterations in urine pH can allow drugs to be trapped in the urine and excreted

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27
Q

Drug Form

A

oral drugs must be lipophilic and small in size to penetrate the GI mucosa

Tablets must dissolve into smaller particles

Liquids do not have the dissolution step

Enteric coating alters dissolution and/or absorption

Decreased gastric motility lengthens absorption time

Increased gastric motility shortens absorption time (may pass into feces)

Presence of food may interfere with dissolution and absorption of certain drugs

May be detoxified by the liver due to the first pass effect

28
Q

First Pass Effect

A

All blood that circulates to the small intestine must travel through the liver on its way to the systemic circulation via the hepatic portal system

This system allows the liver to remove potential toxins before they reach the general circulation

Some drugs are recognized as foreign substances and may be removed, thus preventing them from reaching the general circulation and tissues

Drugs that have an extensive first-pass effect are usually not recommended for PO use!

29
Q

What water affinity must parenteral drugs be in?

A

hydrophilic form

30
Q

Anything that interferes with drug diffusion from the administration site or alters blood flow to the injection site will delay absorption; what are they?

A

Limited blood flow at the injection site will slow absorption (fat vs. muscle)

Temperature will affect blood flow to the administration site (vasoconstriction vs. vasodilation)

Some drugs are formulated for delayed absorption (repository/depot injections)

Other drugs may affect blood flow and absorption

31
Q

Patient factors that affect absorption are:

A

Age

Young animals may not have well developed GI tracts and less active enzyme systems

General health

Fever may increase movement of drug molecules

GI disease (vomiting/diarrhea) hinders absorption

Metabolic rate

Higher metabolic rates may cause more rapid drug metabolism and elimination

Genetic factors

Individual/species variation in response to drugs

Cats have a more rapid GI transit time

Sex

Males and females have different body fat compositions that may influence the absorption, and distribution of drugs

32
Q

Distribution

A

the physiologic movement of drugs from the systemic circulation to the target tissues or site of action

33
Q

Factors that affect distribution include

A

Membrane permeability and tissue perfusion

34
Q

Protein Binding

A

Some drugs bind to proteins (albumin) in the blood and the large drug-protein complexes become trapped in the circulation

Animals with low protein levels will have less protein available for binding and more free drug available for the target tissues

35
Q

Volume of Distribution

A

Drug concentration in the blood will lower if the drug has a large volume to distribute through

Diseases that produce extra body fluid (edema, ascites) will have less drug concentration in the blood and tissues due to a greater volume of distribution

36
Q

Biotransformation or Metabolism

A

the chemical alteration of the drug molecules into metabolites by the body cells of the animal so that:

drugs are changed chemically into a “metabolite” form that can be active, inactive and/or toxic

metabolites are generally more ionized, hydrophilic and less chemically active so that they can be eliminated from the body

37
Q

What is the primary organ of biotransformation; list the other places

A

The primary organ of biotransformation is the liver (cytochrome P450 of the hepatocytes)

Other locations include the lungs, skin, intestinal tract, kidney, nervous system

38
Q

What are the four main pathways of biotransformation?

A

Oxidation, reduction, hydrolysis, conjugation

39
Q

Factors affecting biotransformation include

A

Plasma protein binding

Less plasma protein binding allows excretion

Storage in tissue and fat

Liver disease

Less cytochrome P450

Species/Individual variation

Cats have decreased ability to form glucuronic acid

Route of administration

Some drugs cannot be given orally

Body temperature

Enzymes are temperature dependant

Age of patient

Very young or old due to liver status

Rumen pH changes with age

Nutritional status

40
Q

Excretion or elimination

A

removal of drug from the body. Most drugs are excreted via the kidney into the urine.

41
Q

Other routes of elimination include

A

the liver (first pass effect)

the lungs (anesthetic gases)

sweat/salivary glands (used in forensics)

milk (residue concerns for food safety)

intestinal tract (via bile and feces)

incorporation into hair, nails, hooves

42
Q

Mechanisms of renal excretion include:

A
  • Glomerular filtration (Non-selective,Highly dependant upon blood flow/pressure)
  • Tubular secretion (Active transport across the convoluted tubule membrane, Moves molecules from blood into urine filtrate)
  • Tubular reabsorption (Occurs in the loop of Henle, Drugs that are highly lipid soluble/non-ionized will have increased reabsorption)
43
Q

Factors affecting excretion:

A

renal perfusion

clearance rate

half life

patient age

concurrent disease

percent of functioning nephrons

types of drugs/secondary drugs (concurrent diuretic use)

tubular reabsorption

44
Q

Steady state

A

point at which drug accumulation and elimination are balanced

45
Q

What ways can drugs interact with eachother

A
  • Altered absorption (One drug affects another drug’s absorption) - Competition for plasma proteins (Two drugs may both bind to plasma, One displacing the other) - Altered excretion (drugs that act directly on the kidney may affect excretion) - Altered metabolism (drugs may need the same enzymes for biotransformation and decrease the rate of metabolism)
  • Microsomal enzyme induction - some drugs cause liver enzymes to be more efficient (The drug’s rate of biotransformation is increased, Must monitor and increase dose periodically to maintain therapeutic blood levels)
  • Tolerance – decreased response to a drug (
46
Q

What are the two different types of tolerance?

A

Metabolic – drug metabolized quicker with chronic use
Cellular – “down regulation” or decreased cellular receptor response with repeated use

47
Q

Where are the recepters drugs interact with located?

A

Receptors are three dimensional proteins or glycoproteins located located on:

Cell membrane surface

Cell cytoplasm

Within the nucleus

48
Q

Tissue affinity and receptor sites

A

cell receptors bind to the drug molecules and then a response occurs through a structural-activity relationship between the drug and receptor

49
Q

Affinity

A

the strength of binding between a drug and its receptor (measure of affinity is called the dissociation constant or KD)

50
Q

Efficacy

A

the degree to which a drug has an exact fit to the receptor or produces the desired effect

51
Q

Agonist

A

a drug that binds to a cell receptor and causes an action (has both affinity and efficacy)

52
Q

Lock and Key comparison

A

similar to how drugs and receptors interact

53
Q

Partial Agonist/Antagonist

A

A drug that binds to a cell receptor but has only partial effect (has affinity but only partial efficacy)

54
Q

Antagonist

A

a drug that inhibits or blocks the response of the receptor site (has affinity but NO efficacy)

55
Q

Competative Antagonist

A

competes for the same receptor

56
Q

Non-competative Antagonist

A

binds to a different site than the agonist, but changes the shape of the agonist’s receptor, preventing the drug’s action

57
Q

Non-Receptor Mediated Action

A

there are no cellular receptors with which the drug interacts(Osmotics and Chelators)

58
Q

Osmotics

A

pull water from tissues and cells due to a molecular size or chemical effect that attracts water

59
Q

Chelators

A

types of compounds used as drugs that physically combine with ions (e.g. Ca, Mg, Cl) or other specific compounds to produce their effects

60
Q

Drug Interaction

A

an altered pharmacologic response to a drug that caused by the presence of a second (or more) drug

61
Q

Adverse Drug Event

A

harm to a patient caused by drug administration for therapy or diagnosis

62
Q

What are some causes of Adverse Drug Events?

A
  • Due to medication errors such as wrong drug, wrong dose, wrong patient, etc.
  • Due to an “adverse drug reaction” from the inherent properties of the drug itself such as poor drug quality or purity, reaction to the drug carrier, etc.
  • Photosensitivity
  • Other types of adverse drug reactions include vomiting, diarrhea, impaired hearing, organ damage (liver, kidney, heart), infertility/abortion, cancer, anaphylactic shock and death.
63
Q

Photosensitivity Adverse Drug reaction

A

drugs that cause changes in the skin

64
Q

Idiosyncratic Adverse Drug reaction

A

an unusual or unexpected reaction

65
Q

Pharmaceutic Interaction

A
  • physical or chemical reactions that occur as a result of mixing drugs in a syringe or container
  • may precipitate or be altered when mixed and chemically inactivate the drug(s) or cause an adverse reaction
66
Q

when should adverse drug reactions be reported

A

ALWAYS
All adverse drug reactions should be reported to the drug manufacturer or FDA.

the drug company is obligated to report the adverse reaction to the FDA

VET - Pharm (17 decks)

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